In order to study the functional role of the molecular constituents of desmosomes in intercellular adhesion, we will begin by isolating desmosomes in quantity and preparing antibodies against them and their individual macromolecular components. By utilizing these antibodies (or Fab's made from them) both the label desmosome constituents and to perturb cellular interaction in vitro and in vivo, we hope to determine the degree to which desmosomal elements are involved in cellular recognition and adhesion, and the dynamics of adhesion-formation and turnover, a process of great importance in cellular migration. Through these techniques, we will determine whether immunologically cross-reacting components exist in other junction-types (especially other adherens junctions) or free on the cell surface, and in desmosomes of other tissues. By applying anti-desmosomal antibodies (in solution, in liposomes or on beads) to cells, we will determine whether the mirror-symmetry of desmosomes results from their assembly by a mutual adhesive patching phenomenon between apposed cell surfaces. Using autoantibodies of patients afflected with pemphigus and lupus erythematosis, we will attempt to identify within desmosomes at least some of the antigenic targets attacked in these disorders. Finally, we will determine whether rabbits induced to form antibodies against specific desmosomal components can serve as animal models for the study of these two autoimmune diseases.